1. Technical Field
The present invention relates to novel compounds which modulate the activity of RORC and their use as medicaments.
2. Background Information
RORγt (retinoid-related orphan receptor γt) (also referred to herein as “RORC”) is a transcription factor belonging to the steroid hormone receptor superfamily (reviewed in Jetten 2006. Adv. Dev Biol. 16:313-355.). RORγt has been identified as a transcriptional factor that is required for the differentiation of T cells and secretion of Interluekin 17 (IL-17) from a subset of T cells termed Th17 cells (Ivanov, Cell 2006, 126, 1121-1133). The rationale for the use of a RORγt targeted therapy for the treatment of chronic inflammatory diseases is based on the emerging evidence that Th17 cells and the cytokine IL-17 contribute to the initiation and progression of the pathogenesis of several autoimmune diseases including psoriasis, ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis and Crohn's disease (reviewed in Miossec, Nature Drug Discovery 2012, 11, 763-776; see also Khan et al., Bioorganic & Medicinal Chemistry Letters 23 (2013), 532-536). The outcome of recent clinical trials with nuetralizing antobodies to IL-17 and its receptor IL-17RA (Leonardi 2012, New England Journal of Medicine, 366, 1190-1199; Papp 2012, New England Journal of Medicine 366, 1181-1189) in psoriasis highlight the role of IL-17 in the pathogenesis of this disease. As such, attenuation of IL-17 secretion from activated Th17 T cells via inhibtion of RORγt may offer similar therapeutic benefit.